a b s t r a c tMore than 100 transthyretin (TTR) variants are associated with hereditary amyloidosis. Approaches for TTR amyloidosis that interfere with any step of the cascade of events leading to fibril formation have therapeutic potential. In this study we tested (À)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, as an inhibitor of TTR amyloid formation. We demonstrate that EGCG binds to TTR ''in vitro" and ''ex vivo" and that EGCG inhibits TTR aggregation ''in vitro" and in a cell culture system. These findings together with the low toxicity of the compound raise the possibility of using EGCG in a therapeutic approach for familial amyloidotic polyneuropathy, the most frequent form of hereditary TTR amyloidosis.
Structured summary:MINT-7294529: TTR (uniprotkb:P02766) and TTR (uniprotkb:P02766) bind (MI:0407) by comigration in non-denaturing gel electrophoresis (MI:0404)
The thermodynamics of the interaction between a hydrophobically modified cationic polyelectrolyte and an
anionic surfactant (sodium dodecyl sulfate, SDS) has been investigated by microcalorimetry, conductivity,
and UV−vis spectrophotometry. The polyelectrolyte employed was a newly synthesized polymer (D40OCT30)
based on dextran having pendant N-(2-hydroxypropyl)-N,N-dimethyl-N-octylammonium chloride groups
randomly distributed along the polymer backbone with a degree of substitution (DS) of 28.1%. The interaction
between D40OCT30 and SDS was found to be very strong because of the introduction of ionic and hydrophobic
moieties on the backbone of the dextran polymer. The aggregation concentration of polyelectrolyte−SDS
complex (CACcomplex) was derived from the curves of variation of the observed enthalpy, solution conductivity,
and optical dispersion with SDS concentrations. The results show that these values obtained from different
methods are coincident and increase with D40OCT30 concentration. A mechanism of interaction is proposed
and discussed in detail in the text. The total interaction enthalpies were derived from the observed enthalpy
curves. The results indicate that the total interaction process is entropy-driven. From the calorimetric and
turbidity measurements, the partial phase diagram that describes the dependence of the phase boundary on
polymer alkyl side chain concentration is also deduced.
The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-9)] with liposomes was studied by differential scanning calorimetry (DSC), circular dichroism (CD), and quasi-elastic light scattering (QELS). The study was carried out with large unilamellar vesicles (LUVs) of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoylsn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a binary mixture of DMPC/DMPG, in a wide range of peptide-to-lipid (P:L) molar ratios (0 to 1:7). DSC results indicate that, for both peptides, the interaction depends on membrane composition, with very different behavior for zwitterionic and anionic membranes. CD data show that, although the two peptides have different secondary structures in buffer (random coil for CA(1-7)M(2-9) and predominantly -sheet for CA(1-8)M(1-18)), they both adopt an R-helical structure in the presence of the membranes. Overall, results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, which gives place to aggregation in the gel phase and precipitation after a threshold peptide concentration. In the case of zwitterionic membranes, a progressive surface coverage with peptide molecules destabilizes the membrane, eventually leading to membrane disruption. Moreover, delicate modulations in behavior were observed depending on the peptide.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.